Implications of an Underlying Beckwith-Wiedemann Syndrome for Wilms Tumor Treatment Strategies.

Beckwith-Wiedemann Syndrome (BWS) is a pediatric overgrowth disorder involving a predisposition to embryonal tumors. Most of the tumors associated with BWS occur in the first 8-10 years of life, and the most common is Wilms tumor (WT). BWS clinical heterogeneity includes subtle overgrowth features or even silent phenotypes, and WT may be the presenting symptom of BWS.

Design of a multiplex ligation-dependent probe amplification assay for SLC20A2: identification of two novel deletions in primary familial brain calcification.

Primary familial brain calcification (PFBC) is a rare disease characterized by brain calcifications that mainly affect the basal ganglia, thalamus, and cerebellum. Among the four autosomal-dominant genes known to be associated with the disease, SLC20A2 pathogenic variants are the most common, accounting for up to 40% of PFBC dominant cases; variants include both point mutations, small insertions/deletions and intragenic deletions. Over the last 7 years, we have collected a group of 50 clinically diagnosed PFBC patients, who were screened for single nucleotide changes and small insertions/deletions in SLC20A2 by Sanger sequencing.

Reduction of CFU-GM and circulating hematopoietic progenitors in a subgroup of children with chronic neutropenia associated with severe infections and delayed recovery.

Myelopoiesis was evaluated in 66 pediatric patients with chronic neutropenia who were positive for anti-neutrophil antibodies (median age at diagnosis: 11 months, median neutrophil count at diagnosis: 419/μl). Other causes of neutropenia were excluded. Bone marrow morphology, clonogenic tests and/or the peripheral blood CD 34+ cell count, and apoptotic rate were evaluated in 61 patients with neutropenia lasting > 12 months or severe infections.

Ribosomal RNA analysis in the diagnosis of Diamond-Blackfan Anaemia.

Diamond-Blackfan anaemia (DBA) is an inherited disease characterized by pure erythroid aplasia that has been tagged as a 'ribosomopathy'. We report a multi-centre study focused on the analysis of rRNA processing of 53 Italian DBA patients using capillary electrophoresis analysis of rRNA maturation of the 40S and 60S ribosomal subunits. The ratio of 28S/18S rRNA was higher in patients with mutated ribosomal proteins (RPs) of the small ribosomal subunit.

Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis.

Diamond Blackfan anemia (DBA), a syndrome primarily characterized by anemia and physical abnormalities, is one among a group of related inherited bone marrow failure syndromes (IBMFS) which share overlapping clinical features. Heterozygous mutations or single-copy deletions have been identified in 12 ribosomal protein genes in approximately 60% of DBA cases, with the genetic etiology unexplained in most remaining patients. Unlike many IBMFS, for which functional screening assays complement clinical and genetic findings, suspected DBA in the absence of typical alterations of the known genes must frequently be diagnosed after exclusion of other IBMFS.

Loss of GATA-1 full length as a cause of Diamond-Blackfan anemia phenotype.

Mutations in the hematopoietic transcription factor GATA-1 alter the proliferation/differentiation of hemopoietic progenitors. Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins.

The spectrum of non-classical Diamond-Blackfan anemia: a case of late beginning transfusion dependency associated to a new RPL5 mutation.

Diamond Blackfan anemia typically presents in infants and is often associated with many kinds of malformations. Severity of anemia often needs transfusional support in the first months of life. We describe here a patient with Diamond Blackfan anemia related to a RPL5 mutation.

High frequency of ribosomal protein gene deletions in Italian Diamond-Blackfan anemia patients detected by multiplex ligation-dependent probe amplification assay.

Diamond-Blackfan anemia is an autosomal dominant disease due to mutations in nine ribosomal protein encoding genes. Because most mutations are loss of function and detected by direct sequencing of coding exons, we reasoned that part of the approximately 50% mutation negative patients may have carried a copy number variant of ribosomal protein genes. As a proof of concept, we designed a multiplex ligation-dependent probe amplification assay targeted to screen the six genes that are most frequently mutated in Diamond-Blackfan anemia patients: RPS17, RPS19, RPS26, RPL5, RPL11, and RPL35A.

Cleft palate and ADULT phenotype in a patient with a novel TP63 mutation suggests lumping of EEC/LM/ADULT syndromes into a unique entity: ELA syndrome.

Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare condition belonging to the group of ectodermal dysplasias caused by TP63 mutations. Its clinical phenotype is similar to ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) and limb-mammary syndrome (LMS), and differs from these disorders mainly by the absence of cleft lip and/or palate. We report on a 39-year-old patient who was found to be heterozygous for a c.

The ribosomal basis of Diamond-Blackfan Anemia: mutation and database update.

Diamond-Blackfan Anemia (DBA) is characterized by a defect of erythroid progenitors and, clinically, by anemia and malformations. DBA exhibits an autosomal dominant pattern of inheritance with incomplete penetrance. Currently nine genes, all encoding ribosomal proteins (RP), have been found mutated in approximately 50% of patients.

Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations.

Background: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation.

Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer.

Background: Diamond-Blackfan anaemia (DBA) is a rare inherited red cell hypoplasia characterised by a defect in the maturation of erythroid progenitors and in some cases associated with malformations. Patients have an increased risk of solid tumors. Mutations have been found in several ribosomal protein (RP) genes, i.

Remittent hyperammonemia in congenital portosystemic shunt.

Congenital portosystemic shunts (PSS) are rare vascular anomalies with different gross anatomy. Persistent patent ductus venosus (PDV) represents an uncommon cause of intrahepatic PSS. The diagnosis of this condition may not be obvious because of its wide spectrum of clinical manifestations, ranging from asymptomatic to life-threatening disease.

HDR syndrome: a novel "de novo" mutation in GATA3 gene.

Human GATA3 haploinsufficiency leads to HDR (hypoparathyroidism, deafness, and renal dysplasia) syndrome. The development of a specific subset of organs in which this transcription factor is expressed appears exquisitely sensitive to gene dosage. We report on a 14-year-old patient with symptomatic hypoparathyroidism, sensorineural bilateral deafness, unilateral renal dysplasia, bilateral palpebral ptosis, and horizontal nystagmus.

A new database for ribosomal protein genes which are mutated in Diamond-Blackfan Anemia.

Mutations in ribosomal proteins RPS19, RPS24 and RPS17 have been reported in Diamond-Blackfan Anemia (DBA), an autosomal dominant disease characterised by pure red cell aplasia. DBA is the prototype of ribosomapathies: a protein synthesis defect in a tissue with a high cellular turnover is considered the cause of the erythroid progenitor failure. We have created the Diamond-Blackfan Anemia mutation database to curate and record DBA gene mutations, together with their functional consequences and clinical phenotypes.

R298Q mutation of p63 gene in autosomal dominant ectodermal dysplasia associated with arrhythmogenic right ventricular cardiomyopathy.

Mutations in the p63 gene have been identified in five types of syndromic ectodermal dysplasias (EDs) with overlapping phenotypes: Ectrodactyly-Ectodermal dysplasia-Clefting (EEC syndrome, MIM 604292), Ankyloblepharon-Ectodermal dysplasia-Clefting (AEC syndrome, MIM 106260) [3], Acro-Dermato-Ungueal-Lacrimal-Tooth (ADULT syndrome, MIM 103285), Rapp-Hodgkin (RHS syndrome, MIM 129400) and Limb-Mammary (LMS syndrome, MIM 603543) [2]. In all those conditions congenital heart defects have been only occasionally found and to date, arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) has never been observed in patients affected by p63-related ectodermal dysplasia [9]. Here we describe for the first time this association.

RPS19 mutations in patients with Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is an inherited disease characterized by pure erythroid aplasia. Thirty percent (30%) of patients display malformations, especially of the hands, face, heart, and urogenital tract. DBA has an autosomal dominant pattern of inheritance.

Progressive external ophthalmoplegia and vision and hearing loss in a patient with mutations in POLG2 and OPA1.

Objective: To describe the clinical features, muscle pathological characteristics, and molecular studies of a patient with a mutation in the gene encoding the accessory subunit (p55) of polymerase gamma (POLG2) and a mutation in the OPA1 gene.

Design: Clinical examination and morphological, biochemical, and molecular analyses.

Setting: Tertiary care university hospitals and molecular genetics and scientific computing laboratory.

Co-inherited mutations of Fas and caspase-10 in development of the autoimmune lymphoproliferative syndrome.

Background: Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder characterized by defective function of Fas, autoimmune manifestations that predominantly involve blood cells, polyclonal accumulation of lymphocytes in the spleen and lymph nodes with lymphoadenomegaly and/or splenomegaly, and expansion of TCRalphabeta+ CD4/CD8 double-negative (DN) T cells in the peripheral blood. Most frequently, it is due to Fas gene mutations, causing ALPS type Ia (ALPS-Ia). However, other mutations, namely of the FasL gene (ALPS-Ib) and the caspase-10 gene (ALPS-II) are occasionally detected, whereas some patients do not present any known mutations (ALPS-III).

The broad spectrum of autoimmune lymphoproliferative disease: molecular bases, clinical features and long-term follow-up in 31 patients.

Autoimmune lymphoproliferative disorders, including autoimmune lymphoproliferative syndrome (ALPS) and Dianzani autoimmune lymphoproliferative disease (DALD), are inherited defects of the Fas apoptotic pathway characterized by lymphoid accumulation and autoimmune manifestations. We report the molecular, clinical, immunologic features and the long-term progress of 31 patients. Four carried Fas gene mutations and one also displayed a caspase 10 polymorphism that probably contributed to the phenotype.